Study On The Alleviate Alzheimer’s Disease Mechanism Of Zijuan Pu’er Tea In C.elegans

Alzheimer’s disease(AD)is a kind of neurodegenerative disease,its main pathological feature is the deposition of senile plaques in the brain and the entanglement of nerve fibers,but the specific pathogenesis of AD is not clear.With the acceleration of population aging process,the number of patients with Alzheimer’s disease is increasing year by year,so it is urgent to develop a drug to reduce the incidence of Alzheimer’s disease and delay the occurrence and development of Alzheimer’s disease.At present,treatment of Alzheimer’s disease drugs is mainly cholinesterase inhibitors,such drugs can only alleviate the symptoms of patients,but can’t achieve the basic goal.So researchers are committed to the development of new drugs to treat AD.A lot of studies have shown that the natural products with antioxidant effect may have the effect of treatment of Alzheimer’s disease.Natural product as a drug derived from natural have good application prospect.Therefore,this paper has screened drug on the natural products of anti-Alzheimer’s disease.Although the pathogenesis of Alzheimer’s disease is not yet clear,there are several hypotheses recognized by the public,especially the Aβ cascade hypothesis.So the drug screening model of AD was Caenorhabditis elegans(C.elegans)Aβ model.After a series of screening,we found that many natural products have good effect,and we chose Zijuan Pu’ er tea as the main research object.We designed three doses of the drug : 0.1mg/ml,0.2mg/ml and 0.4mg/ml.For the CL4176 transgenic nematode,the three concentrations all had the effect of delaying the paralysis of nematodes.This effect showed concentration dependence.Therefore,we chose 0.4mg/ml of Zijuan Pu’er tea to carry out the mechanism of the study.We tested the effect of EGCG and proanthocyanidins,and found that they did not play a major role.At first,we detected the effect level of Zijuan Pu’er tea,and found that 0.4 mg/ml Zijuan Pu’er tea did not affect the mRNA level of Aβ in CL4176 but could inhibit the deposition of Aβ.It indicated that the drug play a role in the post-transcriptional level.Secondly,we pretreated the CL4176 nematode with 0.4mg/ml Zijuan Pu’er tea and found that theadministration group still had the effect on delaying the paralysis of nematodes.Therefore,we detected the mRNA level of a number of transcription factors related to stress resistance in Caenorhabditis elegans by qPCR,and we found that sir2.1 was significantly up-regulated.Thirdly,we used the TJ356 nematode to test the effect of0.4 mg/ml of Zijuan Pu’er tea on DAF-16 translocation,and found that 0.4 mg/ml of Zijuan Pu’er tea could promote the nuclear translocation of DAF-16 after administration.We used SOD::GFP C.elegans to further confirm the need of daf-16 transcription activity to against oxidative stress.According to the increase of the oxidative stress caused by Aβ,and the ROS content and SOD activity would change when treated with Zijuan Pu’er tea,we hypothesized that Zijuan Pu’er tea might improve the ability to resist oxidative stress.Finally,we detected the poisons of the drug and found that Zijuan Pu’er tea could play a role in delaying the paralysis of nematodes under the safe dose.In conclusion,we screened the drug of anti-Alzheimer’s disease by C.elegans.Zijuan Pu’er tea was able to inhibit the toxicity of Aβ and significantly delay the paralysis of nematode.This inhibition may be related to the ability of decrease the oxidative stress induced by Aβ and the inhibition of the Aβ deposition.